CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression.
Mod Pathol
; 28(1): 57-68, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-24947144
ABSTRACT
Recent molecular advances have identified a novel, clinically aggressive subgroup of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high-grade nuclear features, including vesicular chromatin and nucleoli, patchy clear cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases, including 6 newly identified cases, 2 with paired metastases. Given our prior observation of trisomy 8 in these tumors, we assayed for amplification and expression of MYC (c-Myc) and representative downstream targets. Trisomy 8 was detected in 5/7 testable cases, with further amplification of MYC locus in 6/7 testable cases and immunohistochemical expression of MYC in 10/10. The canonical MYC transcriptional target, p21, but not MTDH, was differentially expressed compared with Ewing sarcomas. Given prior observation of induction of ETS-family transcription factors by the fusion oncoprotein, we assayed and identified highly prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary regarding use of these immunostains in prospective case workup, whereas the prevalent MYC amplification may represent a therapeutically targetable oncogenic pathway in CIC-DUX sarcomas.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Tecidos Moles
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Genes myc
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Sarcoma de Células Pequenas
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Proteínas Proto-Oncogênicas c-ets
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Mod Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos